2-(Phenylsulfonyl)quinoline N-hydroxyacrylamides as potent anticancer agents inhibiting histone deacetylase

Hsueh Yun Lee; Chih Yi Chang; Chih Jou Su; Han Li Huang; Samir Mehndiratta; Yuh Hsuan Chao; Chia Ming Hsu; Sunil Kumar; Ting Yi Sung; Yi Zhen Huang; Yu Hsuan Li; Chia Ron Yang; Jing Ping Liou

doi:10.1016/j.ejmech.2016.06.023

2-(Phenylsulfonyl)quinoline N-hydroxyacrylamides as potent anticancer agents inhibiting histone deacetylase

Hsueh Yun Lee, Chih Yi Chang, Chih Jou Su, Han Li Huang, Samir Mehndiratta, Yuh Hsuan Chao, Chia Ming Hsu, Sunil Kumar, Ting Yi Sung, Yi Zhen Huang, Yu Hsuan Li, Chia Ron Yang, Jing Ping Liou

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27 引文斯高帕斯（Scopus）

摘要

This study reports the design and synthesis of 2-(phenylsulfonyl)quinoline N-hydroxyacrylamides (8a–k). Structure-activity relationship studies focusing on regio-effect of N-hydroxyacrylamide moiety and influence of the sulfonyl linker revealed that N-hydroxy-3-[3-(quinoline-2-sulfonyl)-phenyl]-acrylamide (8f) showed remarkable enzymatic and cellular activity. The GI₅₀values of 8f for HL-60, HCT116, PC-3, and A549 cells were found to be 0.29, 0.08, 0.15, and 0.27 μM, respectively. The compounds are therefore more potent than FDA approved PXD-101 and SAHA. They also have an effect on the acetylation degree of histone H3 and α-tubulin. In in vivo studies, 8f showed marked inhibition of the growth of HCT116 xenografts.

原文	英語
頁（從 - 到）	92-101
頁數	10
期刊	European Journal of Medicinal Chemistry
卷	122
DOIs	https://doi.org/10.1016/j.ejmech.2016.06.023
出版狀態	已發佈 - 2016

ASJC Scopus subject areas

藥物發現
藥理
有機化學

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10.1016/j.ejmech.2016.06.023

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Lee, H. Y., Chang, C. Y., Su, C. J., Huang, H. L., Mehndiratta, S., Chao, Y. H., Hsu, C. M., Kumar, S., Sung, T. Y., Huang, Y. Z., Li, Y. H., Yang, C. R., & Liou, J. P. (2016). 2-(Phenylsulfonyl)quinoline N-hydroxyacrylamides as potent anticancer agents inhibiting histone deacetylase. European Journal of Medicinal Chemistry, 122, 92-101. https://doi.org/10.1016/j.ejmech.2016.06.023

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title = "2-(Phenylsulfonyl)quinoline N-hydroxyacrylamides as potent anticancer agents inhibiting histone deacetylase",

abstract = "This study reports the design and synthesis of 2-(phenylsulfonyl)quinoline N-hydroxyacrylamides (8a–k). Structure-activity relationship studies focusing on regio-effect of N-hydroxyacrylamide moiety and influence of the sulfonyl linker revealed that N-hydroxy-3-[3-(quinoline-2-sulfonyl)-phenyl]-acrylamide (8f) showed remarkable enzymatic and cellular activity. The GI50values of 8f for HL-60, HCT116, PC-3, and A549 cells were found to be 0.29, 0.08, 0.15, and 0.27 μM, respectively. The compounds are therefore more potent than FDA approved PXD-101 and SAHA. They also have an effect on the acetylation degree of histone H3 and α-tubulin. In in vivo studies, 8f showed marked inhibition of the growth of HCT116 xenografts.",

keywords = "2-(Phenylsulfonyl)quinoline, Anticancer agents, Histone deacetylase inhibitors",

author = "Lee, {Hsueh Yun} and Chang, {Chih Yi} and Su, {Chih Jou} and Huang, {Han Li} and Samir Mehndiratta and Chao, {Yuh Hsuan} and Hsu, {Chia Ming} and Sunil Kumar and Sung, {Ting Yi} and Huang, {Yi Zhen} and Li, {Yu Hsuan} and Yang, {Chia Ron} and Liou, {Jing Ping}",

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doi = "10.1016/j.ejmech.2016.06.023",

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AU - Lee, Hsueh Yun

AU - Chang, Chih Yi

AU - Su, Chih Jou

AU - Huang, Han Li

AU - Mehndiratta, Samir

AU - Chao, Yuh Hsuan

AU - Hsu, Chia Ming

AU - Kumar, Sunil

AU - Sung, Ting Yi

AU - Huang, Yi Zhen

AU - Li, Yu Hsuan

AU - Yang, Chia Ron

AU - Liou, Jing Ping

PY - 2016

Y1 - 2016

N2 - This study reports the design and synthesis of 2-(phenylsulfonyl)quinoline N-hydroxyacrylamides (8a–k). Structure-activity relationship studies focusing on regio-effect of N-hydroxyacrylamide moiety and influence of the sulfonyl linker revealed that N-hydroxy-3-[3-(quinoline-2-sulfonyl)-phenyl]-acrylamide (8f) showed remarkable enzymatic and cellular activity. The GI50values of 8f for HL-60, HCT116, PC-3, and A549 cells were found to be 0.29, 0.08, 0.15, and 0.27 μM, respectively. The compounds are therefore more potent than FDA approved PXD-101 and SAHA. They also have an effect on the acetylation degree of histone H3 and α-tubulin. In in vivo studies, 8f showed marked inhibition of the growth of HCT116 xenografts.

AB - This study reports the design and synthesis of 2-(phenylsulfonyl)quinoline N-hydroxyacrylamides (8a–k). Structure-activity relationship studies focusing on regio-effect of N-hydroxyacrylamide moiety and influence of the sulfonyl linker revealed that N-hydroxy-3-[3-(quinoline-2-sulfonyl)-phenyl]-acrylamide (8f) showed remarkable enzymatic and cellular activity. The GI50values of 8f for HL-60, HCT116, PC-3, and A549 cells were found to be 0.29, 0.08, 0.15, and 0.27 μM, respectively. The compounds are therefore more potent than FDA approved PXD-101 and SAHA. They also have an effect on the acetylation degree of histone H3 and α-tubulin. In in vivo studies, 8f showed marked inhibition of the growth of HCT116 xenografts.

KW - 2-(Phenylsulfonyl)quinoline

KW - Anticancer agents

KW - Histone deacetylase inhibitors

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2-(Phenylsulfonyl)quinoline N-hydroxyacrylamides as potent anticancer agents inhibiting histone deacetylase

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